The purpose of this study is to determine (a) whether the requirements for agonist-specific desensitization using plasma membranes reflect the mechanism for such desensitization in intact cells. This will be tested for in the glucagon-stimulated adenylyl cyclase of liver using hepatocytes and plasma membranes and the catecholamine-sensitive adenylyl cyclase of the S49 lymphoma cell line, and (b) determine the nature of modifications, during agonist-specific desensitization, that renders the receptor non-functional in both the liver and S49 system. In addition, the mechanism of agonist-independent divalent cation-dependent loss or hormonal stimulation in the liver and the role of phospholipid turnover during agonist-specific desensitization in S49 cells will be studied.